Objective: To find potential correlates of placebo response in adults with attention-deficit/hyperactivity disorder (ADHD) and gain insights into why placebo response may be high in clinical trials.

Method: Post hoc analysis of placebo data from 2 randomized controlled trials of osmotic-release oral system (OROS) methylphenidate in adults with ADHD defined according to the Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition: the Long-Acting Methylphenidate in Adults with ADHD (LAMDA-I) study (2005–2006, 5 weeks, n=95) and the LAMDA-II study (2008–2009, 13 weeks, n=97). The primary efficacy measure was the Conners’ Adult ADHD Rating Scale-observer rated, short version (CAARS:O-SV). Predictors of CAARS:O-SV change were assessed using a random-intercepts model with demographic and disease-related parameters as independent variables. Sensitivity analyses were conducted using the CAARS self-report (CAARS:S-S) and a categorical response criterion (improvement of >30% in CAARS:O-SV), and in subjects who completed the study.

Results: In LAMDA-I, mean±SD change in CAARS:O-SV was –7.6±9.9 with placebo and –11.9±10.6 with OROS methylphenidate. Higher baseline CAARS score (P=.007) and lower educational achievement (P=.014) were significantly associated with greater improvement in placebo-treated subjects. In LAMDA-II, mean±SD change in CAARS:O-SV was –10.4±11.0 and –14.1±10.7 in subjects receiving placebo and OROS methylphenidate, respectively. Variables significantly associated with greater placebo response were higher baseline CAARS:O-SV (P=.019), shorter time since ADHD diagnosis (P<.045), and younger age (P=.014). None of the sensitivity analyses challenged the outcomes.

Conclusions: Possible predictors of placebo response in adults with ADHD include higher severity of ADHD symptoms, younger age, shorter time since diagnosis, and lower educational level.